ZGRF1 is a 5'-3' DNA helicase that functions as a critical mediator of homologous recombination-based repair of replication-blocking DNA lesions 1. The protein is recruited to DNA damage sites where it directly stimulates RAD51-mediated strand exchange activity, promoting recombinational repair after RAD51 recruitment without loading RAD51 itself 1. ZGRF1 additionally positively regulates EXO1-mediated DNA end resection and facilitates RPA2 recruitment to damage sites 2. Biochemically, ZGRF1 catalyzes Holliday junction branch migration and D-loop dissociation, physically interacting with RAD51-RAD54 complexes 1. ZGRF1-deficient cells accumulate chromosome 4 following replication perturbation and show sensitivity to mitomycin C and camptothecin, demonstrating its essential role in genomic stability 1. Beyond DNA repair, ZGRF1 promotes G2/M checkpoint initiation 2 and meiotic recombination, with ZGRF1 loss resulting in reduced fertility through decreased meiotic crossovers 3. Genetic variants in ZGRF1 have been associated with adiposity measures in Hispanic populations and identified in patients with neonatal hypoxic ischaemic encephalopathy, suggesting broader physiological relevance 45. These findings position ZGRF1 as a potential therapeutic target in cancer due to its role in DNA repair.